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c-Src: bridging the gap between phosphorylation- and acidification-induced gap junction channel closure
1Natural Products and Cancer Biology Program, Cancer Research Center, University of Hawaii at Manoa, Honolulu, HI 96813, USA. aflau@crch.hawaii.edu
Summary
Intracellular acidification disrupts astrocyte communication by altering connexin43 phosphorylation and protein interactions. This affects intercellular communication, crucial for brain function.
Area of Science:
- Cell Biology
- Neuroscience
- Biochemistry
Background:
- Gap junctions facilitate direct cell-to-cell communication via connexin proteins.
- Mutations in connexins are linked to skin and neurosensory disorders.
- Intercellular communication is regulated by pH, phosphorylation, and protein interactions.
Purpose of the Study:
- To explore how intracellular acidification impacts astrocyte intercellular communication.
- To detail the molecular events disrupting gap junction function during ischemia/hypoxia.
Main Methods:
- This perspective reviews molecular mechanisms.
- Focuses on events triggered by intracellular acidification in astrocytes.
Main Results:
- Acidification alters connexin43 (Cx43) phosphorylation.
- Beta-actin binding to Cx43 is disrupted.
- Cx43 interacts with c-Src, ERK1/2, and MKP1.
Conclusions:
- Intracellular acidification triggers complex molecular changes that interrupt astrocyte gap junction communication.
- These alterations involve Cx43 modifications and interactions with signaling kinases and phosphatases.